One of the main problems in patients with carcinoma of the prostate is the pain suffered from skeletal metastases. Several radionuclides such as Sr-89 which concentrate in such metastases are used to alleviate the pain and its effect on the quality of life. The aim of this project is to ablate the skeletal secondary deposits. To do this we give greatly increased activities (so far up to 4000 MBq compared with the more usual approximately 2000 MBq) of Re-l86 HEDP with peripheral blood stem cell support (PBSCS) to overcome the effects of bone marrow irradiation by uptake of the radiopharmaceutical in normal bone. So far it seems that the upper levels of activity we have given are more effective in ablating metastases not visible on the bone scintigram rather than ablating those already visible. In a Phase I activity escalation protocol we are treating patients with skeletal metastases which have escaped hormonal control. On finishing the Phase I study at the end of April 2000 we will have determined the maximum activity which can be administered safely and will use this level of activity in the Phase II study which is the subject of this grant application. In this Phase II study we will measure the number of new metastases at three to twelve months and analyze the behavior of the metastases originally visible. Based on the results of this study we will then design a new study comparing the effect of high dose unsealed source therapy with peripheral blood stem cell support in patients with rising prostate specific serum antigen but no visible metastases with those receiving standard therapy alone. We will analyze the data already acquired from the Phase I study to attempt to determine a metastatic dose response relationship. From this we will be able to evaluate the possibility of giving even higher activities of a shorter half-life bone seeker such as Sm-153. We would then be able to give higher doses/dose rates yet have lower residual radiation at 12 days post treatment when the peripheral blood stem cells are re-infused.